title: What lies within: novel strategies in immunotherapy for non-small cell lung cancer.
abstract: Immunotherapy has become an increasingly important therapeutic strategy for those with cancer, with phase III studies demonstrating survival advantages in melanoma and castration-resistant prostate cancer. Non-small cell lung cancer (NSCLC) is a promising target for the next generation of immune-based strategies. In this article, we examine the current state of the art in lung cancer immunotherapy, including vaccines that specifically target lung tumor antigens and immune checkpoint antibodies such as antiprogrammed death 1 (anti-PD-1). Both approaches harness innate immunity against tumors by suppressing tumor-induced immune paresis. Methods. To identify relevant clinical trials of immunotherapy in NSCLC, PubMed and Medline databases were searched using the terms "immunotherapy" and "NSCLC," and several other therapy-specific search terms (e.g., PD-1, NSCLC). Additionally, abstracts presented at international lung cancer symposia, the American Society of Clinical Oncology annual meeting, and the European Society of Medical Oncology annual meeting between 2005 and 2013 were evaluated. Results. Large international phase III trials of NSCLC vaccines have completed accrual in both the adjuvant and metastatic disease settings. Results of the START study were disappointing, but results from other studies are still awaited. Immune checkpoint modulation has shown promise, with separate phase I studies of the anti-PD-1 antibody, nivolumab, and anti-PD-L1 antibody, MPDL3280A, demonstrating good tolerance and durable responses for certain patients with NSCLC who were heavily pretreated. Conclusions. Immune-based strategies have shown initial promise for early- and advanced-stage NSCLC. Validating these findings in randomized studies and discovering durable biomarkers of response represent the next challenges for investigation.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Forde
authors.forename: Kim A
authors.initials: KA
authors.lastname: Reiss
authors.forename: Amer M
authors.initials: AM
authors.lastname: Zeidan
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000628:therapy*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D019496:Cancer Vaccines
keywords: CTLA4; Immune checkpoint; Immunotherapy; Lung cancer; NSCLC; PD-L1; PD1; Vaccine